Monoclonal antibodies have been used in earlier studies in this laboratory to identify and characterize the transferrin receptors of human and murine cells. Transferrin receptors are associated with active cell growth and are selectively expressed on some tumors in vivo. Monoclonal antibodies have been obtained that block receptor function and inhibit tumor cell growth in vitro. This work is being developed in two directions. Mouse L-cell transformants have been obtained that express the human transferrin receptor on their cell surface, and this approach has recently led to the isolation of the human transferrin receptor gene. Studies of the genetic regulation of the transferrin receptor and its relationship to cell growth and differentiation are now feasible. The other aspect of the project is to investigate the effects of monoclonal antibodies that block transferrin receptor function on the growth of tumor cells in vivo. In the past year, it has been shown that a rat IgM monoclonal antibody against the murine transferrin receptor can inhibit the growth of a syngeneic leukemia, SL-2, in AKR/J mice. Both inhibition of growth of the primary subcutaneous tumor and prolonged survival of tumor-bearing mice were demonstrated. There was no evidence of toxicity associated with administration of the antibody. The distribution of transferrin receptors on murine hematopoietic stem cells has also been investigated. (CS)